Alzheimer’s

Life lessons learned in the CIRM summer intern program

/ Kevin McCormack / Leave a comment
SPARK poster session; Photo by Esteban Cortez

When I was in high school I spent my summers working in a shoe shop and playing soccer with my mates. It never occurred to me that I could do something really  worthwhile with that time. So, when I meet the high school students who took part in the California Institute for Regenerative Medicine’s SPARK program I realized I had wasted a lot of time.

For those not familiar with SPARK, it stands for Summer Program to Accelerate Regenerative Medicine Knowledge. It’s a summer program offering high school students a chance to work in a world-class stem cell and gene therapy research facility. The quality of the work they do is truly remarkable. By the end of the summer they are doing projects that many full-time researchers would be proud of.

As part of that program the students also must write blogs and post photos and videos to Instagram to chart their progress. The quality of that work is equally impressive. Last week we posted items about the two best blogs from the students. But there were so many other fine entries that we thought it would be worthwhile to highlight elements of those.

For instance, Ricardo Rodriguez at Charles R. Drew University had some interesting observations on life, even when it’s not always working out the way you planned:

Ricardo Rodriguez: Photo by Esteban Cortez

“Cancer is not life going wrong so much as it is life changing. If mutation is random, then so is life. That beautiful randomness that drives evolution and extinction, change and stagnation, life and death, and for you to think that that part of your body could be simple in any way, whether it be simply evil, simply inconvenient, simply structured, is simply hilarious. There is beauty in your body’s complexity, adaptability, and resilience, and these attributes are not barred from any part of your life.”

Mindy Rodriguez at Beckman City of Hope says she learned valuable lessons from working with mice, creatures she previously considered scary, dirty and vicious, but later came to like:

“The CIRM SPARK program reinforced the value of facing my fears by exploring the unknown and most importantly taught me to be comfortable with the uncomfortable. In both cases, I found that it is our response to fear that shapes who we are. We can either run away from the thing that scares us or take each moment as a learning opportunity, embracing change over comfort.”

Manvi Ketireddy at work at UC Davis

Manvi Ketireddy at UC Davis had a similar experience, learning to accept things not working out.

“A researcher must be persistent and have the ability to endure lots of failures. I think that is what I love about research: the slight possibility of discovery and answers amid constant defeat is one of the greatest challenges to exist. And boy, do I love challenges.”

Ameera Ali in the lab (fish not included)

Ameera Ali at Sanford Burnham Prebys says she had struggled for years to decide on a career direction, but the internship gave her a fresh perspective on it all.

“Growing up, I never really knew what I wanted to do for a living, and I think that’s because I wanted to do everything. In kindergarten I wanted to be a paleontologist. In 5th grade I wanted to be the CEO of The San Diego Union Tribune, and in 9th grade I wanted to be a physicist at NASA. By 10th grade I was having an existential crisis about what to do with my life, and so began the search for my purpose at the ripe old age of 15.

So now, writing this blog, I never thought I’d end up spending so much of my time in a room filled floor to ceiling with fish tanks. You might be wondering, how does one end up going from physicist to fish farmer? Well, I’m not completely sure to be honest, but it’s been a very fun and interesting experience nonetheless.”

She says by the end she says what initially felt like mundane chores were actually moments worth celebrating.

“These aquatic friends have taught me a lot of valuable life lessons, like being appreciative of the little things in life, caring for others and see things from a different perspective, and realizing that

working in a biology lab allows me to explore my passions, be creative, and be a mother to hundreds of fish children on the side.”

SPARK attracts students from all over California, and it’s that diversity that makes it so important.

Alexa Gastelum

My name is Alexa Gastelum and I am from a small border town called Calexico. It is located in the Imperial Valley around two hours away from San Diego. I found out about this Internship from my Math teacher and Mesa Coordinator. They discussed what it was about, and I immediately knew that I wanted to apply. I have always been interested in doing labs and researching so I knew that it would be the perfect opportunity for me. It is not normal to be presented with an opportunity like this from where I’m from because it is a small and low-income town. When I told my family about this internship they were very supportive. They agreed that I needed to apply for it since it was an extremely good opportunity. Even though I would need to spend my summer away from my hometown, they were okay with it because they knew that I could not miss out on the opportunity. I decided to write my personal statement on a disease that hit close to home with my family which was Alzheimer’s. It is a disease that runs in my family and my uncle passed from it. I believe that this is what sparked my interest because I wanted to understand how it worked and how it affects the brain.

At the SPARK event Alexa told me her grandmother was so proud of her for being accepted at the program that she was going around town telling everyone about it. Her grandmother, and all the other grandmothers and mothers and fathers, had every reason to be proud of these students. They are remarkable young people and we look forward to following their careers in the years to come.

Two common viruses could trigger Alzheimer’s disease

/ Katie Sharify / Leave a comment

Researchers from Tufts University and the University of Oxford have found that two common viruses —the varicella zoster and herpes simplex viruses— could trigger Alzheimer’s disease.

Varicella zoster (VZV) is an extremely common virus causes which causes chickenpox. Once cured of the first infection, the virus tends to linger in peripheral nerves where they remain dormant. When these dormant viruses are reactivated, they cause shingles.

HSV-1, the subtype of the herpes simplex virus, causes both oral and genital herpes. It is a very common infection, affecting nearly 4 million people worldwide under the age of 50 years. The American Sexual Health Organization estimates that around one in two adults has oral herpes in the United States. 

Cytokines are produced in response to VZV. Cytokines are part of a healthy immune system. These small proteins help control the growth and activity of your blood cells and immune cells. Cytokines tell your immune system to do its job. But when too many cytokines are released, it can cause your immune system to go into overdrive, resulting in cytokine storm.

In their findings, published in the Journal of Alzheimer’s Disease, researchers found that when VZV infect neurons, they trigger an inflammatory response due to this overproduction of cytokines. This inflammatory response in turn awakens the herpes simplex viruses which typically lie dormant and harmless in the brain. With both viruses now active, inflammation throughout the brain is aggravated, potentially leading to the formation of plaque and the slow deterioration of neurons—both hallmarks of Alzheimer’s.

The study’s leading author, Dana Cairns, along with her team of collaborators gathered data by using lab grown cultures of brain nerve, or neural, stem cells. They found that infecting neurons with varicella zoster alone was not enough to trigger Alzheimer-like properties. However, when the herpes simplex was already lying-in wait, varicella zoster initiated a series of events that resulted in plaques, tangled fibers and brain damage.

“It’s a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble,” explains Cairns. One of her collaborators, Oxford’s Ruth Itzhaki, was one of the first scientists to suggest a link between herpes infections and Alzheimer’s.

The California Institute for Regenerative Medicine (CIRM) has already invested almost $35 million in 21 different Alzheimer’s projects. In addition, we are committed to investing at least $1.5 billion in treatments that target conditions affecting the brain and central nervous system (CNS), including Alzheimer’s. 

Study reveals new evidence of key mechanism in Alzheimer’s

/ Esteban Cortez / 1 Comment

In California, 690,000 people aged 65 and older are living with Alzheimer’s, a degenerative brain disease and the most common form of dementia. In the United States, 5.8 million people aged 65 and older live with Alzheimer’s disease. Alzheimer’s affects memory, thinking and behavior and symptoms eventually grow in severity to interfere with daily tasks.  

There is no cure for Alzheimer’s, which is why Rutgers scientists are examining human brain cells in mice to identify a pivotal mechanism that could result in a potential therapy for the disease. In a recent study, the Rutgers team found more clear-cut evidence of how the destructive proteins linked to Alzheimer’s disease attack human brain cells and destroy surrounding tissue. 

The researchers studied human brain immune cells injected into the brains of specially bred immunodeficient mice, creating what they called a human-mouse chimera. The researchers detailed what happened to specialized immune brain cells known as microglia after those cells were exposed to tau proteins—destructive substances believed to be involved in Alzheimer’s and other severe human brain diseases. 

“This provided an unprecedented opportunity to investigate the role of human microglia in brains as well as the cognitive impairment seen in Alzheimer’s Disease and Down syndrome, a genetic disorder with a high risk of developing Alzheimer’s disease,” said Peng Jiang, an associate professor in the Department of Cell Biology and Neuroscience at the Rutgers School of Arts and Sciences. 

By studying the process in the newly-developed brain—which allowed human cells to grow, develop and mature with appropriate functions—the scientists were able to witness and analyze a cellular brain attack that has been largely elusive up to this point. 

In autopsies, scientists have been able to study the brains of people who died from Alzheimer’s and have seen residues of tau proteins and cellular changes. The human-mouse brain chimera has allowed the Rutgers team to extract and see human cells in the actual process of deterioration. 

The mice in the study were specially bred to be immunodeficient so that they could receive implanted human cells without rejecting them due to normal immune defenses.  The immunodeficient mice were injected with human microglial cells and, later, with tau proteins, which are linked to the development of the brain disease. 

“Since microglial cells are one of the first cell responders when something goes wrong in the brain, we believe the changes we saw to be significant,” said Mengmeng Jin, a postdoctoral researcher in the Department of Cell Biology and Neuroscience at Rutgers and first author on the study. 

The California Institute for Regenerative Medicine (CIRM) is committed to investing at least $1.5 billion—more than double what CIRM funded between 2006 and 2020—in treatments that target conditions affecting the brain and central nervous system (CNS), including Alzheimer’s. 

Read the source release about the study here.  

Stem Cell Agency Board Invests in 19 Discovery Research Programs Targeting Cancers, Heart Disease and Other Disorders

/ Kevin McCormack / 2 Comments

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Dr. Judy Shizuru, Stanford University

While stem cell and gene therapy research has advanced dramatically in recent years, there are still many unknowns and many questions remaining about how best to use these approaches in developing therapies. That’s why the governing Board of the California Institute for Regenerative Medicine (CIRM) today approved investing almost $25 million in 19 projects in early stage or Discovery research.

The awards are from CIRM’s DISC2 Quest program, which supports  the discovery of promising new stem cell-based and gene therapy technologies that could be translated to enable broad use and ultimately, improve patient care.

“Every therapy that helps save lives or change lives begins with a researcher asking a simple question, “What if?”, says Dr. Maria T. Millan, the President and CEO of CIRM. “Our Quest awards reflect the need to keep supporting early stage research, to gain a deeper understanding of stem cells work and how we can best tap into that potential to advance the field.”

Dr. Judy Shizuru at Stanford University was awarded $1.34 million to develop a safer, less-toxic form of bone marrow or hematopoietic stem cell transplant (HCT). HCT is the only proven cure for many forms of blood disorders that affect people of all ages, sexes, and races worldwide. However, current methods involve the use of chemotherapy or radiation to destroy the patient’s own unhealthy blood stem cells and make room for the new, healthy ones. This approach is toxic and complex and can only be performed by specialized teams in major medical centers, making access particularly difficult for poor and underserved communities.

Dr. Shizuru proposes developing an antibody that can direct the patient’s own immune cells to kill diseased blood stem cells. This would make stem cell transplant safer and more effective for the treatment of many life-threatening blood disorders, and more accessible for people in rural or remote parts of the country.

Lili Yang UCLA Broad Stem Cell Research Center: Photo courtesy Reed Hutchinson PhotoGraphics

Dr. Lili Yang at UCLA was awarded $1.4 million to develop an off-the-shelf cell therapy for ovarian cancer, which causes more deaths than any other cancer of the female reproductive system.

Dr. Yang is using immune system cells, called invariant natural killer T cells (iNKT) to attack cancer cells. However, these iNKT cells are only found in small numbers in the blood so current approaches involve taking those cells from the patient and, in the lab, modifying them to increase their numbers and strength before transplanting them back into the patient. This is both time consuming and expensive, and the patient’s own iNKT cells may have been damaged by the cancer, reducing the likelihood of success.

In this new study Dr. Yang will use healthy donor cord blood cells and, through genetic engineering, turn them into the specific form of iNKT cell therapy targeting ovarian cancer. This DISC2 award will support the development of these cells and do the necessary testing and studies to advance it to the translational stage.

Timothy Hoey and Tenaya Therapeutics Inc. have been awarded $1.2 million to test a gene therapy approach to replace heart cells damaged by a heart attack.

Heart disease is the leading cause of death in the U.S. with the highest incidence among African Americans. It’s caused by damage or death of functional heart muscle cells, usually due to heart attack. Because these heart muscle cells are unable to regenerate the damage is permanent. Dr. Hoey’s team is developing a gene therapy that can be injected into patients and turn their cardiac fibroblasts, cells that can contribute to scar tissue, into functioning heart muscle cells, replacing those damaged by the heart attack.

The full list of DISC2 Quest awards is:

APPLICATION NUMBERTITLE OF PROGRAMPRINCIPAL INVESTIGATORAMOUNT
  DISC2-13400  Targeted Immunotherapy-Based Blood Stem Cell Transplantation    Judy Shizuru, Stanford Universtiy  $1,341,910    
  DISC2-13505  Combating Ovarian Cancer Using Stem Cell-Engineered Off-The-Shelf CAR-iNKT Cells    Lili Yang, UCLA  $1,404,000
  DISC2-13515  A treatment for Rett syndrome using glial-restricted
neural progenitor cells  		  Alysson Muotri, UC San Diego  $1,402,240    
  DISC2-13454  Targeting pancreatic cancer stem cells with DDR1 antibodies.    Michael Karin, UC San Diego  $1,425,600  
  DISC2-13483  Enabling non-genetic activity-driven maturation of iPSC-derived neurons    Alex Savtchenko, Nanotools Bioscience  $675,000
  DISC2-13405  Hematopoietic Stem Cell Gene Therapy for Alpha
Thalassemia  		  Don Kohn, UCLA    $1,323,007  
    DISC2-13507  CAR T cells targeting abnormal N-glycans for the
treatment of refractory/metastatic solid cancers  		  Michael Demetriou, UC Irvine  $1,414,800  
  DISC2-13463  Drug Development of Inhibitors of Inflammation Using
Human iPSC-Derived Microglia (hiMG)  		  Stuart Lipton, Scripps Research Inst.  $1,658,123  
  DISC2-13390  Cardiac Reprogramming Gene Therapy for Post-Myocardial Infarction Heart Failure    Timothy Hoey, Tenaya Therapeutics  $1,215,000  
  DISC2-13417  AAV-dCas9 Epigenetic Editing for CDKL5 Deficiency Disorder    Kyle Fink, UC Davis  $1,429,378  
  DISC2-13415  Defining the Optimal Gene Therapy Approach of
Human Hematopoietic Stem Cells for the Treatment of
Dedicator of Cytokinesis 8 (DOCK8) Deficiency  		  Caroline Kuo, UCLA  $1,386,232  
  DISC2-13498  Bioengineering human stem cell-derived beta cell
organoids to monitor cell health in real time and improve therapeutic outcomes in patients  		  Katy Digovich, Minutia, Inc.  $1,198,550  
  DISC2-13469  Novel antisense therapy to treat genetic forms of
neurodevelopmental disease.  		  Joseph Gleeson, UC San Diego  $1,180,654  
  DISC2-13428  Therapeutics to overcome the differentiation roadblock in Myelodysplastic Syndrome (MDS)    Michael Bollong, Scripps Research Inst.  $1,244,160  
  DISC2-13456  Novel methods to eliminate cancer stem cells    Dinesh Rao, UCLA  $1,384,347  
  DISC2-13441  A new precision medicine based iPSC-derived model to study personalized intestinal fibrosis treatments in
pediatric patients with Crohn’s diseas  		  Robert Barrett Cedars-Sinai  $776,340
  DISC2-13512  Modified RNA-Based Gene Therapy for Cardiac
Regeneration Through Cardiomyocyte Proliferation		  Deepak Srivastava, Gladstone Institutes  $1,565,784
  DISC2-13510  An hematopoietic stem-cell-based approach to treat HIV employing CAR-T cells and anti-HIV broadly
neutralizing antibodies  		  Brian Lawson, The Scintillon Institute  $1,143,600  
  DISC2-13475  Developing gene therapy for dominant optic atrophy using human pluripotent stem cell-derived retinal organoid disease model    Xian-Jie Yang, UCLA  $1,345,691  

Can regenerative medicine turn back the clock on aging?

/ Kevin McCormack / Leave a comment

One of my favorite phrases is “standing room only”. I got a chance to use it last week when we held a panel discussion on whether regenerative medicine could turn back the clock on aging. The event was at the annual conference of the International Society for Stem Cell Research (ISSCR) and more than 150 people packed into a conference room to hear the debate (so far more than 800 also watched a live stream of the event.)

It’s not surprising the place was jammed. The speakers included:

  • Dr. Deepak Srivastava, the President of the Gladstone Institutes, an expert on heart disease and the former President of ISSCR.
  • Dr. Stanley “Tom” Carmichael, Chair of the Department of Neurology at UCLA and an expert on strokes and other forms of brain injury.
  • Adrienne Shapiro, the mother of a daughter with sickle cell disease, a tireless patient advocate and supporter of regenerative medicine research, and the co-founder of Axis Advocacy, a family support organization for people with sickle cell.
  • Jonathan Tomas, PhD, JD, the Chair of the CIRM Board.

And the topic is a timely one. It is estimated that as many as 90 percent of the people who die every day, die from diseases of aging such as heart disease, stroke, and cancer. So, what can be done to change that, to not just slow down or stop these diseases, but to turn back the clock, to repair the damage already done and replace cells and tissues already destroyed.

The conversation was enlightening, hopeful and encouraging, but also cautionary.

You can watch the whole event on our Youtube channel.

I think you are going to enjoy it.

Join us to hear how stem cell and gene therapy are taking on diseases of aging

/ Kevin McCormack / Leave a comment

It is estimated that as many as 90 percent of people in industrialized countries who die every day, die from diseases of aging such as heart disease, stroke, and cancer. Of those still alive the numbers aren’t much more reassuring. More than 80 percent of people over the age of 65 have a chronic medical condition, while 68 percent have two or more.

Current medications can help keep some of those conditions, such as high blood pressure, under control but regenerative medicine wants to do a lot more than that. We want to turn back the clock and restore function to damaged organs and tissues and limbs. That research is already underway and we are inviting you to a public event to hear all about that work and the promise it holds.

On June 16th from 3p – 4.30p PST we are holding a panel discussion exploring the impact of regenerative medicine on aging. We’ll hear from experts on heart disease and stroke; we will look at other ground breaking research into aging; and we’ll discuss the vital role patients and patient advocates play in helping advance this work.

The discussion is taking place in San Francisco at the annual conference of the International Society for Stem Cell Research. But you can watch it from the comfort of your own home. That’s because we are going to live stream the event.

Here’s where you can see the livestream: https://www.youtube.com/watch?v=CaUgsc5alDI

And if you have any questions you would like the panel to answer feel free to send them to us at info@cirm.ca.gov

Turning back the clock to make old skin cells young again

/ Kevin McCormack / Leave a comment

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Dr. Diljeet Gill, photo courtesy Babraham Institute, Cambridge UK

Sometimes when I am giving public presentations people ask if stem cells are good for the face. I always say that if stem cells could help improve people’s faces would I look like this. It’s a line that gets a laugh but it’s also true. The ads you see touting stem cells as being beneficial for skin are all using plant stem cells. But now some new research has managed to turn back the clock for skin cells, and it might do a lot more than just help skin look younger.

Back in 2007 Japanese scientist Shinya Yamanaka discovered a way to turn ordinary skin cells back into an embryonic-like state, meaning those cells could then be turned into any other cell in the body. He called these cells induced pluripotent stem cells or iPSCs. Dr. Yamanaka was later awarded the Nobel Prize for Medicine for this work.

Using this work as their starting point, a team at Cambridge University in the UK, have developed a technique that can rewind the clock on skin cells but stop it less than a third of the way through, so they have made the cells younger but didn’t erase their identity as skin cells.

The study, published in the journal ELifeSciences, showed the researchers were able to make older skin cells 30 years younger. This wasn’t about restoring a sense of youthful beauty to the skin, instead it was about something far more important, restoring youthful function to the skin.

In a news release, Dr Diljeet Gill, a lead author on the study, said: “Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

The team proved the potential for their work using fibroblasts, the most common kind of cell found in connective tissues such as skin. Fibroblasts are important because they produce collagen which helps provide support and structure to tissues and also helps in healing wounds. When the researchers examined the rejuvenated skin cells they found they were producing more collagen than cells that had not been rejuvenated. They also saw signs that these rejuvenated cells could help heal wounds better than the old cells.

The researchers also noted that this approach had an effect on other genes linked to age-related conditions, such Alzheimer’s disease and the development of cataracts.

The researchers acknowledge that this is all very early on, but the fact that they were able to make the cells behave and act like younger cells, without losing their identity as skin cells, holds tremendous promise not just for conditions affecting the skin, but for regenerative medicine as a whole.

Dr. Diljeet concluded: “Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.”

How some brilliant research may have uncovered a potential therapy for Alzheimer’s 

/ Kevin McCormack / Leave a comment
Dr. Nicole Koutsodendris, photo courtesy Gladstone Institutes

In the world of scientific research, the people doing clinical trials tend to suck up all the oxygen in the room. They’re the stars, the ones who are bringing potential therapies to patients. However, there’s another group of researchers who toil away in the background, but who are equally deserving of praise and gratitude. 

Dr. Lana Zholudeva, photo courtesy Gladstone Institutes

These are the scientists who do basic or discovery-level research. This is where all great therapies start. This is where a researcher gets an idea and tests it to see if it holds promise. A good idea and a scientist who asks a simple question, “I wonder if…..”  

Dr. Yadong Huang, Photo courtesy Gladstone Institutes

In our latest “Talking ‘Bout (re)Generation” podcast we talk to three researchers who are asking those questions and getting some truly encouraging answers. They are scientists at the Gladstone Institutes in San Francisco: one seasoned scientist and two young post-docs trying to make a name for themselves. And they might just have discovered a therapy that could help people battling Alzheimer’s disease. 

Enjoy the podcast.

  

Raising awareness about mental health

/ Kevin McCormack / Leave a comment

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World Mental Health Day is observed on 10 October every year. It’s a time to try and raise awareness about mental health issues and the impact they have not just on the individual but their family, their community and all of us. The theme for World Mental Health Day 2021 is ‘mental health in an unequal world.’

Dr. Le Ondra Clark Harvey: Photo courtesy CCCBHA

To highlight the issues raised on World Mental Health Day we talked to one of CIRM’s newest Board member, Dr. Le Ondra Clark Harvey. She’s a psychologist and the CEO of the California Council of Community Behavioral Health Agencies (CCCBHA) a statewide advocacy organization representing mental health and substance use disorder non-profit agencies that collectively serve over 750 thousand Californians annually.

What made you want to be on the CIRM Board?

I was recommended to apply for the CIRM Board by a member of CCCBHA, the organization I am privileged to lead and serve. I saw the position as an opportunity to shed light on cognitive disorders that many do not readily think of when they think about stem cell research. The appointment also has personal meaning to me as I have a grandfather who is a cancer survivor and  who has an Alzheimer’s diagnosis.  Breast cancer has also affected women in my family, including myself, and I know that the research that CIRM funds can assist with finding a cure and providing accessible treatment options for all Californians. 

A lot of people might not think that stem cells would have a role in addressing mental health issues, what role do you think they can play?

You are correct, most people do not immediately think of stem cell therapies as a remedy to brain health disorders. However, there are many cognitive disorders and symptoms that can be mitigated, and hopefully someday ameliorated, as a result of stem cell therapies. For example, autism and other developmental disabilities, dementia, Alzheimer’s, Tourette’s and tardive dyskinesia.  

What are the biggest challenges we face in addressing mental health issues in this country?

Stigma remains a significant barrier that impacts the ability to provide – particularly among racially and ethnically diverse communities. In my own practice, I’ve seen how stigma can prevent individuals from entering into care even when access issues have been mitigated. Public awareness campaigns, and culturally specific advocacy efforts and practices must be integrated into treatment models in order to provide individuals with the specific care they need. 

Do you think that the widespread media attention paid to Naomi Osaka and Simone Biles has helped raise awareness about mental health and perhaps also reduced some of the stigma surrounding it?

Yes, I do. Also, the pandemic has opened many individuals eyes, and engendered a sense of empathy, about the prevalence and impact that isolation and loneliness can have on a person. 

Lack of diversity impacts research into Alzheimer’s and dementia

/ Kevin McCormack / Leave a comment

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A National Institutes of Allergy and Infectious Diseases clinical trial admissions coordinator collects information from a volunteer to create a medical record. Credit: NIAID

Alzheimer’s research has been in the news a lot lately, and not for the right reasons. The controversial decision by the Food and Drug Administration (FDA) to approve the drug Aduhelm left many people wondering how, when, or even if it should be used on people battling Alzheimer’s disease. Now a new study is raising questions about many of the clinical trials used to test medications like Aduhelm.

The research, published in the journal Jama Neurology, looked at 302 studies on dementia published in 2018 and 2019. Most of these studies were carried out in North America or Europe, and almost 90 percent of those studied were white.

In an accompanying editorial in the journal, Dr. Cerise Elliott, PhD, of the National Institute on Aging (NIA) in Bethesda, Maryland, and co-authors wrote that this limited the value of the studies: “This, combined with the fact that only 22% of the studies they analyzed even reported on race and ethnicity, and of those, a median 89% of participants were white, reflects the fact that recruitment for research participation is challenging; however, it is unacceptable that studies continue to fail to report participant demographics and that publishers allow such omissions.”

That bias is made all the more glaring by the fact that recent data from the Centers for Disease Control and Prevention shows that among people 65 and older, the Black community has the highest prevalence of Alzheimer’s disease and related dementias (13.8%), followed by Latinx (12.2%), non-Hispanic white (10.3%), American Indian and Alaskan Native (9.1%), and Asian and Pacific Islander (8.4%) populations.

The researchers admitted that the limited sample size – more than 40 percent of the studies they looked at included fewer than 50 patients – could have impacted their findings. Even so this clearly suggests there is a huge divide between the people at greatest risk of developing Alzheimer’s, or some other form of dementia, and the people being studied.

In the editorial, Elliott and his colleagues wrote that without a more diverse and balanced patient population this kind of research: “will continue to underrepresent people most affected by the disease and perpetuate systems that exclude important valuable knowledge about the disease.”


There are more details on this in Medpage Today.

An editorial in the New England Journal of Medicine highlights how this kind of bias is all too common in medical research.

“For years, the Journal has published studies that simply do not include enough participants from the racial and ethnic groups that are disproportionately affected by the illnesses being studied to support any conclusions about their treatment. In the United States, for example, Black Americans have high rates of hypertension and chronic kidney disease, Hispanic Americans have the highest prevalence of nonalcoholic fatty liver disease, Native Americans are disproportionately likely to have metabolic syndrome, and Asian Americans are at particular risk for hepatitis B infection and subsequent cirrhosis, but these groups are frequently underrepresented in clinical trials and cohort studies.”

“For too long, we have tolerated conditions that actively exclude groups from critical resources in health care delivery, research, and education. This exclusion has tragic consequences and undermines confidence in the institutions and the people who are conducting biomedical research. And clinicians cannot know how to optimally prevent and treat disease in members of communities that have not been studied.”

The encouraging news is that, finally, people are recognizing the problem and trying to come up with ways to correct it. The not so encouraging is that it took a pandemic to get us to pay attention.

At CIRM we are committed to being part of the solution. We are now requiring everyone who applies to us for funding to have a written plan on Diversity, Equity and Inclusion, laying out how their work will reflect the diversity of California. We know this will be challenging for all of us. But the alternative, doing nothing, is no longer acceptable.